Systemic immune-inflammation index mediates the association between metabolic dysfunction-associated fatty liver disease and sub-clinical carotid atherosclerosis: a mediation analysis.

Background: Limited research has been conducted to quantitatively assess the impact of systemic inflammation in metabolic dysfunction-associated fatty liver disease (MAFLD) and sub-clinical carotid atherosclerosis (SCAS). The systemic immune-inflammation index (SII), which integrates inflammatory cells, has emerged as a reliable measure of local immune response and systemic inflammation Therefore, this study aims to assess the mediating role of SII in the association between MAFLD and SCAS in type 2 diabetes mellitus (T2DM). Method: This study prospectively recruited 830 participants with T2DM from two centers. Unenhanced abdominal CT scans were conducted to evaluate MAFLD, while B-mode carotid ultrasonography was performed to assess SCAS. Weighted binomial logistic regression analysis and restricted cubic splines (RCS) analyses were employed to analyze the association between the SII and the risk of MAFLD and SCAS. Mediation analysis was further carried out to explore the potential mediating effect of the SII on the association between MAFLD and SCAS. Results: The prevalence of both MAFLD and SCAS significantly increased as the SII quartiles increased (P<0.05). MAFLD emerged as an independent factor for SCAS risk across three adjusted models, exhibiting odds ratios of 2.15 (95%CI: 1.31-3.53, P < 0.001). Additionally, increased SII quartiles and Ln (SII) displayed positive associations with the risk of MAFLD and SCAS (P < 0.05). Furthermore, a significant dose-response relationship was observed (P for trend <0.001). The RCS analyses revealed a linear correlation of Ln (SII) with SCAS and MAFLD risk (P for nonlinearity<0.05). Importantly, SII and ln (SII) acted as the mediators in the association between MAFLD and SCAS following adjustments for shared risk factors, demonstrating a proportion-mediated effect of 7.8% and 10.9%. Conclusion: SII was independently correlated with MAFLD and SCAS risk, while also acting as a mediator in the relationship between MAFLD and SCAS.

Virus-Associated CD8+ T-Cells Are Not Activated Through Antigen-Mediated Interaction Inside Atherosclerotic Lesions.

INTRODUCTION: Viral infections have been associated with the progression of atherosclerosis and CD8+ T-cells directed against common viruses, such as influenza, Epstein-Barr virus, and cytomegalovirus, have been detected inside human atherosclerotic lesions. These virus-specific CD8+ T-cells have been hypothesized to contribute to the development of atherosclerosis; however, whether they affect disease progression directly remains unclear. In this study, we aimed to characterize the activation status of virus-specific CD8+ T-cells in the atherosclerotic lesion. METHODS: The presence, clonality, tissue enrichment, and phenotype of virus-associated CD8+ T-cells in atherosclerotic lesions were assessed by exploiting bulk T-cell receptor-ß sequencing and single-cell T-cell receptor (α and ß) sequencing datasets on human endarterectomy samples and patient-matched blood samples. To investigate if virus-specific CD8+ T-cells can be activated through T-cell receptor stimulation in the atherosclerotic lesion, the immunopeptidome of human plaques was determined. RESULTS: Virus-associated CD8+ T-cells accumulated more in the atherosclerotic lesion (mean=2.0%), compared with patient-matched blood samples (mean=1.4%; P=0.05), and were more clonally expanded and tissue enriched in the atherosclerotic lesion in comparison with nonassociated CD8+ T-cells from the lesion. Single-cell T-cell receptor sequencing and flow cytometry revealed that these virus-associated CD8+ T-cells were phenotypically highly similar to other CD8+ T-cells in the lesion and that both exhibited a more activated phenotype compared with circulating T-cells. Interestingly, virus-associated CD8+ T-cells are unlikely to be activated through antigen-specific interactions in the atherosclerotic lesion, as no virus-derived peptides were detected on HLA-I in the lesion. CONCLUSIONS: This study suggests that virus-specific CD8+ T-cells are tissue enriched in atherosclerotic lesions; however, their potential contribution to inflammation may involve antigen-independent mechanisms.

Dysregulation of micro-RNA 143-3p as a Biomarker of Carotid Atherosclerosis and the Associated Immune Reactions During Disease Progression.

Atherosclerosis commonly remains undiagnosed until disease manifestations occur. The disease is associated with dysregulated micro(mi)RNAs, but how this is linked to atherosclerosis-related immune reactions is largely unknown. A mouse model of carotid atherosclerosis, human APOB100-transgenic Ldlr-/- (HuBL), was used to study the spatiotemporal dysregulation of a set of miRNAs. Middle-aged HuBL mice with established atherosclerosis had decreased levels of miR-143-3p in their carotid arteries. In young HuBL mice, early atherosclerosis was observed in the carotid bifurcation, which had lower levels of miR-15a-5p, miR-143-3p, and miR-199a-3p, and higher levels of miR-155-5p. The dysregulation of these miRNAs was reflected by specific immune responses during atheroprogression. Finally, levels of miR-143-3p were 70.6% lower in extracellular vesicles isolated from the plasma of patients with carotid stenosis compared to healthy controls. Since miR-143-3p levels progressively decrease when transitioning between early and late experimental carotid atherosclerosis, we propose it as a biomarker for atherosclerosis.

Difference of immune cell infiltration between stable and unstable carotid artery atherosclerosis.

Atherosclerotic plaque instability contributes to ischaemic stroke and myocardial infarction. This study is to compare the abundance and difference of immune cell subtypes within unstable atherosclerotic tissues. CIBERSORT was used to speculate the proportions of 22 immune cell types based on a microarray of atherosclerotic carotid artery samples. R software was utilized to illustrate the bar plot, heat map and vioplot. The immune cell landscape in atherosclerosis was diverse, dominated by M2 macrophages, M0 macrophages, resting CD4 memory T cells and CD8 T cells. There was a significant difference in resting CD4 memory T cells (p = 0.032), T cells follicular helper (p = 0.033), M0 (p = 0.047) and M2 macrophages (p = 0.012) between stable and unstable atherosclerotic plaques. Compared with stable atherosclerotic plaques, unstable atherosclerotic plaques had a higher percentage of M2 macrophages. Moreover, correlation analysis indicated that the percentage of naïve CD4 T cells was strongly correlated with that of gamma delta T cells (r = 0.93, p < 0.001), while memory B cells were correlated with plasma cells (r = 0.85, p < 0.001). In summary, our study explored the abundance and difference of specific immune cell subgroups at unstable plaques, which would aid new immunotherapies for atherosclerosis.

Identification of key pathways and genes in carotid atherosclerosis through bioinformatics analysis of RNA-seq data.

While acknowledging carotid atherosclerosis (CAS) as a risk factor for ischemic stroke, reports on its pathogenesis are scarce. This study aimed to explore the potential mechanism of CAS through RNA-seq data analysis. Carotid intima tissue samples from CAS patients and healthy subjects were subjected to RNA-seq analysis, which yielded, 1,427 differentially expressed genes (DEGs) related to CAS. Further, enrichment analysis (Gene Ontology, KEGG pathway, and MOCDE analysis) was performed on the DEGs. Hub genes identified via the protein-protein interaction network (PPI) were then analyzed using TRRUST, DisGeNET, PaGenBase, and CMAP databases. Results implicated inflammation and immunity in the pathogenesis of CAS. Also, lung disease was associated with CAS. Hub genes were expressed in multiple diseases, mainly regulated by RELA and NFKB1. Moreover, three small-molecule compounds were found via the CMAP database for management of CAS; hub genes served as potential targets. Collectively, inflammation and immunity are the potential pathological mechanisms of CAS. This study implicates CeForanide, Chenodeoxycholic acid, and 0317956-0000 as potential drug candidates for CAS treatment.

Profiles of Immune Cell Infiltration in Carotid Artery Atherosclerosis Based on Gene Expression Data.

Since immune infiltration is closely associated with the progression and prognosis of atherosclerosis, we aimed to describe the abundance of 24 immune cell types within atherosclerotic tissues. In the current study, we used the Immune Cell Abundance Identifier (ImmuCellAI), a web-based tool, to estimate the abundance of 24 immune cells based on the microarray profiles of atherosclerotic carotid artery samples to analyze the proportions and the dysregulation of immune cell types within carotid atherosclerosis. We found that atherosclerotic immune cells had a diverse landscape dominated by T cells and myeloid cells and that macrophages and dendritic cells (DCs) showed different abundance in normal and atherosclerotic tissues. Moreover, the expression of macrophages was closely related to the level of the expression of DCs and of exhausted T cells, while the expression of T-helper type 1 (Th1) cells was strongly correlated with the expression of T-helper type 2 (Th2) cells and effector memory cells. Our data confirm a distinct profile of atherosclerosis-infiltrating immune cell subpopulations, which may inspire an immunological direction for research on atherosclerosis.

Nonclassical Monocytes (CD14dimCD16+) Are Associated With Carotid Intima-Media Thickness Progression for Men but Not Women: The Multi-Ethnic Study of Atherosclerosis-Brief Report.

[Figure: see text].

Statin/ezetimibe combination therapy vs statin monotherapy for carotid atherosclerotic plaque inflammation.

ABSTRACT: It remains uncertain whether statin/ezetimibe combination therapy serves as a useful and equivalent alternative to statin monotherapy for reducing atherosclerotic plaque inflammation. The aim of the present study was to compare the effects of statin/ezetimibe combination therapy and statin monotherapy on carotid atherosclerotic plaque inflammation using 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET)/computed tomography (CT) imaging. Data were pooled from 2 clinical trials that used serial 18FDG PET/CT examination to investigate the effects of cholesterol-lowering therapy on carotid atherosclerotic plaque inflammation. The primary outcome was the percent change in the target-to-background ratio (TBR) of the index vessel in the most diseased segment (MDS) at 6-month follow-up. Baseline characteristics were largely similar between the 2 groups. At the 6-month follow-up, the MDS TBR of the index vessel significantly decreased in both groups. The percent change in the MDS TBR of the index vessel (primary outcome) did not differ significantly between the 2 groups (-8.41 ±â€Š15.9% vs -8.08 ±â€Š17.0%, respectively, P = .936). Likewise, the percent change in the whole vessel TBR of the index vessel did not differ significantly between the 2 groups. There were significant decreases in total and LDL cholesterol levels in both groups at follow-up (P < .001). There were no significant correlations between the percent changes in MDS TBR of the index vessel, changes in the lipid, and high-sensitive C-reactive protein levels. The reduction in carotid atherosclerotic plaque inflammation by statin/ezetimibe combination therapy was equivalent to that by the statin monotherapy.

Anticytomegalovirus CD4+ T Cells Are Associated With Subclinical Atherosclerosis in Persons With HIV.

[Figure: see text].

Bioinformatics analysis reveals the landscape of immune cell infiltration and immune-related pathways participating in the progression of carotid atherosclerotic plaques.

Atherosclerosis is a systemic disease associated with inflammatory cell infiltration and activation of immune-related pathways. In our study, we aimed to uncover immune-related changes and explore novel immunological features in the development of carotid atherosclerotic plaques. First, we applied integrated bioinformatics methods, including CIBERSORT and gene set enrichment analysis (GSEA). The gene expression matrices GSE28829, GSE41571, and GSE43292 were obtained from the Gene Expression Omnibus (GEO) dataset. After a series of data pre-processing steps, the resulting combined expression matrices were analysed using the CIBERSORT, GSEA, and Cluster Profiler packages. After the comparison and analysis between the carotid atherosclerotic plaques in the early and advanced stages, we discovered that there is a higher percentage of activated memory CD4 T cells and a lower percentage of resting memory CD4 cells in advanced-stage plaques. Moreover, activation of memory CD4 T cells can promote the development of carotid atherosclerotic plaques. Additionally, FOXP3+ Treg cell maturation can also participate in the progression of carotid plaques.

Six-Gene Signature Associated with Immune Cells in the Progression of Atherosclerosis Discovered by Comprehensive Bioinformatics Analyses.

BACKGROUND: As a multifaceted disease, atherosclerosis is often characterized by the formation and accumulation of plaque anchored to the inner wall of the arteries and causes some cardiovascular diseases and vascular embolism. Numerous studies have reported on the pathogenesis of atherosclerosis. However, fewer studies focused on both genes and immune cells, and the correlation of genes and immune cells was evaluated via comprehensive bioinformatics analyses. METHODS: 29 samples of atherosclerosis-related gene expression profiling, including 16 human advanced atherosclerosis plaque (AA) and 13 human early atherosclerosis plaque (EA) samples from the Gene Expression Omnibus (GEO) database, were analyzed to get differentially expressed genes (DEGs) and the construction of protein and protein interaction (PPI) networks. Besides, we detected the relative fraction of 22 immune cell types in atherosclerosis by using the deconvolution algorithm of "cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT)." Ultimately, based on the significantly changed types of immune cells, we executed the correlation analysis between DEGs and immune cells to discover the potential genes and pathways associated with immune cells. RESULTS: We identified 17 module genes and 6 types of significantly changed immune cells. Correlation analysis showed that the relative percentage of T cell CD8 has negative correlation with the C1QB expression (R = -0.63, p = 0.02), and the relative percentage of macrophage M2 has positive correlation with the CD86 expression (R = 0.57, p = 0.041) in EA. Meanwhile, four gene expressions (CD53, C1QC, NCF2, and ITGAM) have a high correlation with the percentages of T cell CD8 and macrophages (M0 and M2) in AA samples. CONCLUSIONS: In this study, we suggested that the progression of atherosclerosis might be related to CD86, C1QB, CD53, C1QC, NCF2, and ITGAM and that it plays a role in regulating immune-competent cells such as T cell CD8 and macrophages M0 and M2. These results will enable studies of the potential genes associated with immune cells in the progression of atherosclerosis, as well as provide insight for discovering new treatments and drugs.

Potential genes and pathways along with immune cells infiltration in the progression of atherosclerosis identified via microarray gene expression dataset re-analysis.

OBJECTIVE: Atherosclerosis is a chronic inflammatory process characterized by the accumulation and formation of lipid-rich plaques within the layers of the arterial wall. Although numerous studies have reported the underlying pathogenesis, no data-based studies have been conducted to analyze the potential genes and immune cells infiltration in the different stages of atherosclerosis via bioinformatics analysis. METHODS: In this study, we downloaded GSE100927 and GSE28829 from NCBI-GEO database. Gene ontology and pathway enrichment were performed via the DAVID database. The protein interaction network was constructed via STRING. Enriched hub genes were analyzed by the Cytoscape software. The evaluation of the infiltrating immune cells in the dataset samples was performed by the CIBERSORT algorithm. RESULTS: We identified 114 common upregulated differentially expressed genes and 22 common downregulated differentially expressed genes. (adjust p value < 0.01 and log FC ≥ 1). A cluster of 10 genes including CYBA, SLC11A1, FCER1G, ITGAM, ITGB2, CD53, ITGAX, VAMP8, CLEC5A, and CD300A were found to be significant. Through the deconvolution algorithm CIBERSORT, we analyzed the significant alteration of immune cells infiltration in the progression of atherosclerosis with the threshold of the Wilcoxon test at p value <0.05. CONCLUSIONS: These results may reveal the underlying correlations between genes and immune cells in atherosclerosis, which enable us to investigate the novel insights for the development of treatments and drugs.

Glucose-Regulated Protein 78 Autoantibodies Are Associated with Carotid Atherosclerosis in Chronic Obstructive Pulmonary Disease Patients.

Atherosclerosis prevalence is increased in chronic obstructive pulmonary disease (COPD) patients, independent of other risk factors. The etiology of the excess vascular disease in COPD is unknown, although it is presumably related to an underlying (if cryptic) systemic immune response. Autoantibodies with specificity for glucose-regulated protein 78 (GRP78), a multifunctional component of the unfolded protein response, are common in COPD patients and linked to comorbidities of this lung disease. We hypothesized anti-GRP78 autoreactivity might also be a risk factor for atherosclerosis in COPD patients. Carotid intima-medial thickness (cIMT) was measured in 144 current and former smokers by ultrasound. Concentrations of circulating IgG autoantibodies against full-length GRP78, determined by ELISA, were greater among subjects with abnormally increased cIMT (p < 0.01). Plasma levels of autoantibodies against a singular GRP78 peptide segment, amino acids 246-260 (anti-GRP78aa 246-260), were even more highly correlated with cIMT, especially among males with greater than or equal to moderate COPD (r s = 0.62, p = 0.001). Anti-GRP78aa 246-260 concentrations were independent of CRP, IL-6, and TNF-α levels. GRP78 autoantigen expression was upregulated among human aortic endothelial cells (HAECs) stressed by incubation with tunicamycin (an unfolded protein response inducer) or exposure to culture media flow disturbances. Autoantibodies against GRP78aa 246-260, isolated from patient plasma by immunoprecipitation, induced HAEC production of proatherosclerotic mediators, including IL-8. In conclusion, anti-GRP78 autoantibodies are highly associated with carotid atherosclerosis in COPD patients and exert atherogenic effects on HAECs. These data implicate Ag-specific autoimmunity in the pathogenesis of atherosclerosis among COPD patients and raise possibilities that directed autoantibody reduction might ameliorate vascular disease in this high-risk population.

Subclinical cardiovascular disease in HIV controller and long-term nonprogressor populations.

OBJECTIVES: Elite controllers (ECs), viraemic controllers (VCs), and long-term nonprogressors (LTNPs) control HIV viral replication or maintain CD4 T-cell counts without antiretroviral therapy, but may have increased cardiovascular disease (CVD) risk compared to HIV-uninfected persons. We evaluated subclinical carotid and coronary atherosclerosis and inflammatory biomarker levels among HIV controllers, LTNPs and noncontrollers and HIV-uninfected individuals in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS). METHODS: We measured carotid plaque presence and common carotid artery intima-media thickness (IMT) in 1729 women and 1308 men, and the presence of coronary artery calcium and plaque in a subgroup of men. Associations between HIV control category and carotid and coronary plaque prevalences were assessed by multivariable regression analyses adjusting for demographics and CVD risk factors. Serum inflammatory biomarker concentrations [soluble CD163 (sCD163), soluble CD14 (sCD14), galectin-3 (Gal-3), galectin-3 binding protein (Gal-3BP) and interleukin (IL)-6] were measured and associations with HIV control category assessed. RESULTS: We included 135 HIV controllers (30 ECs) and 135 LTNPs in the study. Carotid plaque prevalence and carotid IMT were similar in HIV controllers, LTNPs and HIV-uninfected individuals. HIV controllers and LTNPs had lower prevalences of carotid plaque compared to viraemic HIV-infected individuals. The prevalence of coronary atherosclerosis was similar in HIV controllers/LTNPs compared to HIV-uninfected and viraemic HIV-infected men. Controllers and LTNPs had higher concentrations of sCD163 and sCD14 compared to HIV-uninfected persons. CONCLUSIONS: Subclinical CVD was similar in HIV controllers, LTNPs and HIV-uninfected individuals despite elevated levels of some inflammatory biomarkers. Future studies of HIV controllers and LTNPs are needed to characterize the risk of CVD among HIV-infected persons.

Regulatory T cells suppress the expression of COX-2 in vulnerable plaque.

COX-2 contributes to local inflammation in atherosclerotic lesions. Regulatory T cells (Tregs) enhance the stability of atherosclerotic plaques. The aim of this study was to detect the potential relationship between Tregs and COX-2 in vulnerable plaques. Thirty ApoE -/- mice were fed a high-fat diet, and a silastic perivascular collar was placed around the right common carotid artery to induce vulnerable plaques. Eight weeks after collar placement, the mice were divided randomly into three groups: control, PBS, and Treg groups. Four weeks later, the right common carotid arteries were collected to detect the expression of COX-2. The results showed that Tregs significantly suppressed the expression of COX-2 in vulnerable plaques. In an in vitro experiment, RAW264.7 cells were divided randomly into three groups, which were precultured without T cells or with CD4 + CD25- T cells or Tregs for 48 h with an anti-CD3 antibody; then the cells were stimulated with LPS for 24 h. The RAW264.7 cells were harvested for RT-PCR and western blot assays and the results showed that Tregs downregulated COX-2 expression in RAW264.7 cells. Therefore, Tregs inhibited the expression of COX-2 in vulnerable plaques and macrophages, and COX-2 inhibition may be an important effect of Tregs that results in atherosclerotic plaque stabilization.

Low CD4 Cell Counts Are Associated with Carotid Plaque and Intima-Media Thickness in Virologically Suppressed HIV-Infected Asians Older Than 50 Years.

Information about the prevalence, and risk factors for subclinical atherosclerosis in an Asian HIV-infected population is limited. Carotid intima-media thickness (cIMT) is one predictor for the risk of cardiovascular disease (CVDs) and mortality. We evaluated the prevalence and risk factors related to carotid atherosclerosis among well-suppressed HIV-infected adults receiving long-term ART from Thailand. This was a cross-sectional study of HIV-infected adults >50 years of age and free from CVDs from Thailand during 1 March 2016 and 30 May 2017. Ultrasonography of the carotid was performed and read by cIMT experienced neurologists who were blinded from the patient care. Subclinical atherosclerosis was defined by carotid plaque or cIMT of the common carotid artery (CCA) >0.9 mm. Totally 316 HIV-infected adults (61% males) were included. Median age was 54.4 years and 15.8% were diabetic, 40.2% had hypertension, and 12.7% were current smokers. The median duration of ART was 16.3 years and 32% were currently on boosted protease inhibitor. The mean overall cIMT of the common carotid arteries were 0.63 (IQR 0.55-0.72) mm. Men had higher cIMT than women, 0.64 (IQR 0.56-0.76) vs. 0.60 (IQR 0.53-0.70), p = .03. Overall, 3.8% had cIMT >0.9 mm and 24.4% had carotid plaque. From the multivariate logistic regression analysis, age per 1 year increase [odds ratio (OR) 1.06; 95% confidence interval (CI) 1.003-1.12; p = .04] and nadir CD4 < 200 cells/mm3 (OR 1.8; 95%CI 1.02-3.18, p = .04) were significantly associated with subclinical atherosclerosis. High-sensitivity C-reactive protein was not associated with subclinical atherosclerosis. In this well-suppressed HIV-infected Aging Asian cohort with relatively low prevalence of current smokers, 26.9% of them had subclinical atherosclerosis. Advanced age and low nadir CD4 cell count were significantly associated with subclinical atherosclerosis. Given that approximately a quarter of the patients had carotid plaques, longitudinal studies to evaluate the development of future overt coronary artery disease and stroke are warranted.

Cholesterol Crystals Induce Coagulation Activation through Complement-Dependent Expression of Monocytic Tissue Factor.

Cholesterol crystals (CC) are strong activators of complement and could potentially be involved in thromboinflammation through complement-coagulation cross-talk. To explore the coagulation-inducing potential of CC, we performed studies in lepirudin-based human whole blood and plasma models. In addition, immunohistological examinations of brain thrombi and vulnerable plaque material from patients with advanced carotid atherosclerosis were performed using polarization filter reflected light microscopy to identify CC. In whole blood, CC exposure induced a time- and concentration-dependent generation of prothrombin fragment 1+2 (PTF1.2), tissue factor (TF) mRNA synthesis, and monocyte TF expression. Blocking Abs against TF abolished CC-mediated coagulation, thus indicating involvement of the TF-dependent pathway. Blockade of FXII by corn trypsin inhibitor had a significant inhibitory effect on CC-induced PTF1.2 in platelet-free plasma, although the overall activation potential was low. CC exposure did not induce platelet aggregation, TF microparticle induction, or TF on granulocytes or eosinophils. Inhibition of complement C3 by CP40 (compstatin), C5 by eculizumab, or C5aR1 by PMX53 blocked CC-induced PTF1.2 by 90% and reduced TF+ monocytes from 18-20 to 1-2%. The physiologic relevance was supported by birefringent CC structures adjacent to monocytes (CD14), TF, and activated complement iC3b and C5b-9 in a human brain thrombus. Furthermore, monocyte influx and TF induction in close proximity to CC-rich regions with activated complement were found in a vulnerable plaque. In conclusion, CC could be active, releasable contributors to thrombosis by inducing monocyte TF secondary to complement C5aR1 signaling.

Body mass index and glucocorticoid dose contribute to subclinical atherosclerosis in Korean patients with systemic lupus erythematosus: A prospective 4 year follow-up study.

AIM: Patients with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease owing to an immunological abnormality, along with traditional risk factors. We found that carotid artery intima-media thickness (cIMT) and plaque were associated with age, body mass index (BMI) and disease activity in a previous study 4 years ago. Our aim was to identify risk factors associated with progression of subclinical atherosclerosis in SLE. METHODS: We assessed cIMT and plaque using Doppler ultrasonography in 61 Korean women with SLE who were enrolled in the previous study 4 years ago. RESULTS: The mean cIMT of the patients was 0.39 ± 0.09 mm; 11 patients had carotid plaques, which was similar to the results of the previous study. Twenty-one patients had increased cIMT, and new carotid plaque had developed in seven patients. Patients with increased cIMT had a lower BMI and took fewer non-steroidal anti-inflammatory drugs and higher 4 year cumulative glucocorticoid dose than patients without increased cIMT. The 4 year cumulative glucocorticoid dose was higher in patients with carotid plaque than in those without. On multivariate regression analysis, BMI (odds ratio [OR] = 0.67, P = 0.034) was associated with increased cIMT, and the 4 year cumulative glucocorticoid dose was associated with increased cIMT (OR = 6.994, P = 0.025) and carotid plaque (OR = 5.651, P = 0.031). CONCLUSION: This prospective follow-up study on cIMT and plaque in patients with SLE showed that low BMI and 4 year cumulative glucocorticoid dose were associated with the progression of subclinical atherosclerosis.